Evaluation of the interaction between insecticide resistance-associated genes and malaria transmission in Anopheles gambiae sensu lato in central Côte d’Ivoire

Abstract

Background There is evidence that the knockdown resistance gene (Kdr) L1014F and acetylcholinesterase-1 gene (Ace-1R) G119S mutations involved in pyrethroid and carbamate resistance in Anopheles gambiae influence malaria transmission in sub-Saharan Africa. This is likely due to changes in the behaviour, life history and vector competence and capacity of An. gambiae. In the present study, performed as part of a two-arm cluster randomized controlled trial evaluating the impact of household screening plus a novel insecticide delivery system (In2Care Eave Tubes), we investigated the distribution of insecticide target site mutations and their association with infection status in wild An. gambiae sensu lato (s.l.) populations. Methods Mosquitoes were captured in 40 villages around Bouaké by human landing catch from May 2017 to April 2019. Randomly selected samples of An. gambiae s.l. that were infected or not infected with Plasmodium sp. were identified to species and then genotyped for Kdr L1014F and Ace-1R G119S mutations using quantitative polymerase chain reaction assays. The frequencies of the two alleles were compared between Anopheles coluzzii and Anopheles gambiae and then between infected and uninfected groups for each species. Results The presence of An. gambiae (49%) and An. coluzzii (51%) was confirmed in Bouaké. Individuals of both species infected with Plasmodium parasites were found. Over the study period, the average frequency of the Kdr L1014F and Ace-1R G119S mutations did not vary significantly between study arms. However, the frequencies of the Kdr L1014F and Ace-1R G119S resistance alleles were significantly higher in An. gambiae than in An. coluzzii [odds ratio (95% confidence interval): 59.64 (30.81–131.63) for Kdr, and 2.79 (2.17–3.60) for Ace-1R]. For both species, there were no significant differences in Kdr L1014F or Ace-1R G119S genotypic and allelic frequency distributions between infected and uninfected specimens (P > 0.05). Conclusions Either alone or in combination, Kdr L1014F and Ace-1R G119S showed no significant association with Plasmodium infection in wild An. gambiae and An. coluzzii, demonstrating the similar competence of these species for Plasmodium transmission in Bouaké. Additional factors including behavioural and environmental ones that influence vector competence in natural populations, and those other than allele measurements (metabolic resistance factors) that contribute to resistance, should be considered when establishing the existence of a link between insecticide resistance and vector competence. Graphical Abstract

Entomological indicators of malaria transmission prior to a cluster-randomized controlled trial of a ‘lethal house lure’ intervention in central Côte d’Ivoire

“…Consistent with recent studies carried out in the area of Bouaké [ 7 , 9 , 13 , 36 ], there was a high frequency of both kdr and ace1 R genes in An. gambiae and An.…”

Small-scale field evaluation of PermaNet® Dual (a long-lasting net coated with a mixture of chlorfenapyr and deltamethrin) against pyrethroid-resistant Anopheles gambiae mosquitoes from Tiassalé, Côte d’Ivoire

“…The existence of multiple mechanisms of resistance in the main vector, Anopheles gambiae sensu lato (s.l.) threatens the efficacy of vector control tools currently used in Côte d'Ivoire, including LLINs [9][10][11]. Meiwald et al [11] found that pyrethroid resistance is associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Anopheles coluzzii in Côte d'Ivoire.…”

“…Meiwald et al [11] found that pyrethroid resistance is associated with significant overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Anopheles coluzzii in Côte d'Ivoire. High allelic frequencies of knock-down resistance (kdr) L1014F mutation (range: 0.46-1), relatively low frequencies of the ace-1R mutation in the acetylcholinesterase gene associated with target-site insensitivity to carbamates and organophosphates (< 0.5), and elevated activity of insecticide detoxifying enzymes (mainly mixed function oxidases (MFOs), esterase and glutathione S-transferase (GST)), have been reported in Côte d'Ivoire [5,7,10]. Recent laboratory (WHO tube and CDC bottle) bioassays against local pyrethroidresistant An.…”

Selection for insecticide resistance can promotePlasmodium falciparuminfection inAnopheles

“…Although some other studies have seen increased Plasmodium infection rates or intensity when at least one kdr allele was present 24,58 , others have identified no association 26,59 , Further, one investigation demonstrated no impact of functional knockdown of para on infection, instead suggesting that the kdr mutation could be in genetic linkage with a gene that impacts immunity 25 . Given our results, such linkage is however unlikely to have occurred in our selection process.…”